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Patented Aug. 28,192d.

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at Brewing Application filed December 15, 18%,

Since the discovery of diethylbarbiturio acid by Emil Fischer frequent and partly successful-attempts have been made to vary the barbituric acid ring. Thus the, ethyl groups were, for instance, replaced partly by the phenylor cy'clohexyl group, partly by higher alkyl groups. Of late years, 'barbituric acids of a great eflicacy have been prepared containing an alkyl group and an alkylene group such for instance as isopropylallyl barbiturio acid and isopropylbromopropenylbarbituric acid. In sp te of numerous and extensive researches on the subject, soporifics'containing an alkyl group with a triple linkage have not-yet been disclosed; This is probablydue tothe-fact that in introducing a radical with'a triple linkage by means of.

theesters' of alkinols (i. e., alcohols containing ,alkinyl radicals, which latter, according to the Genevan Nomenclature as described in Beilsteins 'Handbuch, ed. 4, vol. 1, page 53,

are radicals of the type HCECCH2-),

as for instance propargylbromide or the like, undesirable secondary reactions were to be apprehended in view of the well-known re- Furthermore, the well-known toxicity of numerous bodies, with a tri 1e linkage discouraged the attempts to synt esize bodies of this type.

We have now found that compounds of excellent soporific properties can be obtainedvby 'monoalkylmalonic esters,

wholly or partly replacing in the usual alkylation methods for preparing soporifics the esters of the saturated alcohols by esters of the alkinols. When starting for instance from alkylalkinylmalonic esters are obtained which can be converted by means of urea and alkylates into the corresponding barbituric acid compounds. The same substances may be obtained by causing the esters of the alkinols to act upon According to the process of our present invention, there may also be prepared compounds containing an alkenyl group (i. e., group of the type H C=GHOH and an alkinyl group e. g., allylpropargylbarbituric acid.

' An extensive physiological investigation has proved that the new compounds are soporifics of an excellent eficacy. They are capable of inducing sleep very soon. without other bad after-efiects have the alkyl groups situated in five-position in C. for, 10

Serial No. 155,097, and in Germany June 11, 1925. there being any symptoms indicating intoxications; No dullness fatigue nor any been observed.

The i'pllowing examples serve to illustrate our invention, but they are not intended to limit it thereto:

' l. 17g. of isopropylbarbituric acid are dissolved in 11.3 g. of concentrated caustic soda solution of 35% of 50% strength; there are then added 12 g. of .S-bromopropine (l) and the whole is boiled for five hours. The alcohol is then distilled oh and theresidue is mixed with Water. The separated isopropylpropargylbarbituric acid having np st probably the formula:

washed and recrystallized from water.

The substance thus 0btamed melts at 165 C. and is readily soluble in ether, alcohol and hot water. By the addition. of permanganate the compound is instantaneously decolorized. f When starting from the hydrobromic ester of butin-Q-ol (see Berichte der deutschen chemischen Gesellschaft volume 51, page 383) obtainable from butinol by the action of hydrobromic acid, isopropylmethylpropargylbarblturlc acid is produced by the same process.

2. 41 g. of isopropylbarbituric acid are dissolved in the calculated quantity of caustic soda solution of 5% strength. To this solutlon added 39 g. of isopropenylpropargyl bromide dissolved in 160 com. of alcohol. The mass is allowed to stand for 10 hours at room temperature and is then heated to 50 hours. After having distilled 0d the alcohol in a vacuum,isopropenylpropar- 'gylisopropylbarbituric acid, having most proba ly the formula:

strength and g. of alcohoinardsreaction from 420 o The isopropenylpropargyibromide was produced in the following manner:

Into a solution prepared according, to Grigmagnesium, 210 g. of ethyl bromide and ccm. of ether, are run drop by drop, while cooling with ice, 120 g. of isopropenylacetyiene (obtainable from methyl butinol by the eiiroination of water) dissolved in .90 com. of ether. Atter'Q hours the cooling is discontinued, the mass is stirred first for 6 hours at room temperature and finally for 1 hour under reflux, mass is then again thoroughly cooled and formaldehyde, prepared by heating g. of absolutely dry para-formaldehyde, is then introduced into the etheriul solution of the isopropenylv propargylmagnesiumbromide under reflux and while stirring. t

Miter having decomposed the reaction product with water and acidified with diluted oli uric'acid, the etherial'layer is separated dried over potassium carbonate. After having distilled or? the other the isopropenylpropargylalcohol boils at 6869 C. under 11 mm. pressure. 30

" g. of the alcohol thus obtained are mixed Withof methylene chloride and into this mixture are introduced drop by drop 28.2 g. of phosphorus tribromide while'stirring and well coolin After 2 hours the mass is shaken with ice water and the methylene chloride is distilled ofi. lhe resulting isopropenylpropargylbromide' melts at 65437 C. under 20 mm. pressure.

3. To a solution of 198 g. of diethylmethinbarbituric acid in alcohol is added a solution of 23 g. of sodium in alcohol and the said acidis converted into the sodium salt. There are then added 119 g. of propargylbromideand the wholeis heated in a closed vessel for about 8 hours to C.

After having distilled oft the alcohol, the residue is dissolved in water and the resulting propargyldiethylmethinbarbituric acid, having most probably the :t'ormula phenyl group, but at least one The substance thus obtained melts at l78 and is soluble in alcohol and ether, difiicuitly soluble in water.

We claim: v r p 1. As new products, soporifics being derivatives of barbituric acid and containing at least one allrinyl group in the five position of the barbituric acid ring, corresponding to the general formula: 1

nu-o 9%, 34

nH -oo' wherein X means an alkyl, alirenyl alkinyl or phenyl group, but at least one X being an alkinyl group.

Q. As newproducts, soporifics being derivatives or barbituric acid and containing at least one propargyl group in the five position of the barbituric acid ring, corresponding to the general formula:

wherein X means an alkinyi group.

t. As a new soporific, isopropylisopropenylpropargylbarbituric acid of the tolloi iing formula:

ln testimony whereof, We aiiix our signatures,

is precipitated by means of concentrated hydrochloric acid, then Washed with cold water and repeatedly recrystallized from dilute alcohol.

. DR. MAX BOCKB IUHL.

De. RUD'QLF SGHWAB lDr-i. GUSTAV 

